Multiple sclerosis (MS) is a chronic neurological disease that affects approximately 250,000 individuals in the United States. In a patient afflicted with MS, axons become demyelinated and oligodendrocytes die. Although the clinical course can vary, the most common form is manifested by relapsing neurological deficits, including paralysis, sensory deficits, and visual problems.
In MS and other demyelinating diseases, Schwann cells are generally excluded from areas of demyelination and, following axon damage, regeneration generally fails at Schwann cell-astrocyte boundaries (Carlstedt et al., Brain Res. Bulletin 22:93-102, 1989). Inhibition of Schwann cell migration and boundary formation by astrocytes appears to play a significant part in limiting spontaneous repair processes in the damaged central nervous system (CNS).
In theory, Schwann cells from the peripheral nervous system could be used to replace damaged oligodendrocytes in the CNS. However, the efficacy of such treatment has been limited by poor Schwann cell migration and by boundary formation. When Schwann cells are grafted into the adult CNS, they can migrate along blood vessels and meningeal surfaces, but form boundaries where they meet astrocytes. These boundaries can present an obstacle for regenerating axons. Thus, recruitment of regenerating axons into Schwann cell grafts is frequently poor, and axons remaining in the grafts fail to grow back into CNS tissue unless their target neurons are immediately adjacent (Brecknell et al., Neurosci. 74:775-784, 1996; Liuzzi and Lasak, Science 237:642-645, 1987). Transplanted Schwann cells have been found to be capable of remyelinating central axons of normal (Blakemore, Nature 266:68-69, 1977) or myelin deficient rats (Duncan et al., J. Neurocytol 17:351-360, 1988), but in both of these cases the area of remyelination is limited to the region close to the transplantation site.
Other approaches to developing a definitive treatment for MS have also been largely unsuccessful. Corticosteroids and ACTH may hasten recovery from acute exacerbations, but they do not prevent future attacks, the development of additional disabilities or chronic progression of MS. In addition, the substantial side effects of steroid treatments make these drugs undesirable for long-term use. Other toxic compounds, such as azathioprine, a purine antagonist, cyclophosphamide and cyclosporine have also been used to treat symptoms of MS. Like corticosteroids, however, these drugs are beneficial at most for a short term and are highly toxic. More recently, cytokines such as IFN-.gamma. and IFN-.beta. have been administered in attempts to alleviate the symptoms of MS, but such treatment has led to a clinical exacerbation for some patients. Betaseron has also been employed, but with no effect on the rate of clinical deterioration, and side effects were commonly observed.
Accordingly, there is a need in the art for methods for treating MS that are effective and are not associated with the disadvantages of the present treatments. The present invention fulfills this need and furher provides other related advantages.